Extracellular Vesicles Derived from Human Umbilical Cord Mesenchymal Stem Cells Attenuate Mast Cell Activation.

Abstract

The therapeutic potential of extracellular vesicles isolated from stem cells have been reported in several clinical diseases. Preclinical studies have demonstrated the beneficial effects of extracellular vesicles in the treatment of heart, kidney, liver, brain, and skin injuries. To address the putative therapeutic effects and mechanisms of extracellular vesicles derived from human umbilical cord mesenchymal stem cells on allergic activation in mast cells, we isolated extracellular vesicles from human umbilical cord-derived mesenchymal stem cells (UCMSCs) by tangential-flow filtration methods. The characteristics and identification of UCMSC-derived extracellular vesicles were examined via nanoparticle tracking analysis, transmission electron microscopy and protein marker analysis. Cytokines and tryptase in the cultured supernatant of KU812 cells were analyzed using an ELISA kit. Proteins in the MAPK and STAT5 signaling pathways were detected by Western blotting. This study showed that different doses of UCMSC-derived extracellular vesicles abolish IgE-stimulated KU812 cell activation and reduce the level of NF-κB, which subsequently leads to cell degranulation and the release of IL-1β, TNF-α and IL-6. Additionally, UCMSC-derived extracellular vesicles treatment blunted the IgE-induced signaling proteins p-P38, p-JNK and p-STAT5. Our results revealed a mechanism for anti-inflammation in which extracellular vesicles can affect the activation of mast cells and thus function in allergy regulation.